Silva L C, Simões I G, Lerner F E, Belém G R, de Moraes M E, De Nucci G
Department of Pharmacology, Campinas University, São Paulo, Brazil.
Arzneimittelforschung. 1999 Nov;49(11):920-4. doi: 10.1055/s-0031-1300527.
The aim of the study was to assess the bioequivalence of two different diclofenac (CAS 15307-86-5) formulations (diclofenac free acid suspension as test formulation and diclofenac resinate suspension, Cataflam, as reference formulation) in 24 healthy volunteers. After an overnight fast, the volunteers received a single oral dose (50 mg) of each formulation, following an open, randomized, two-period crossover design, with a fourteen-day washout interval between doses. Serum samples were obtained over a 24-h interval post-dosing, and were analysed for their diclofenac content by HPLC-UV. No adverse effect was reported for any of the formulations administered. Geometric mean test/reference individual ratios were: 92.8% for AUC(0-24 h), 93.2% for AUC(0-infinity), 117.2% for Cmax, 131.0% for Ke and 76.2% for T1/2. The variability of Cmax parameter expressed as CV was greater than 25%. Since the 90% CI for AUC(0-24 h) mean ratio were within the 80-125% interval proposed by the Food and Drug Administration, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for the extent of absorption. Since the European Community Agency accepts a 90% CI for Cmax of 70-143%, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for both the rate and the extent of absorption after single dose administration.
本研究旨在评估两种不同双氯芬酸（CAS 15307-86-5）制剂（双氯芬酸游离酸混悬液作为试验制剂，双氯芬酸树脂酸盐混悬液，凯扶兰，作为参比制剂）在24名健康志愿者体内的生物等效性。经过一夜禁食后，志愿者按照开放、随机、两周期交叉设计，接受每种制剂的单次口服剂量（50毫克），两次给药之间有14天的洗脱期。给药后24小时内采集血清样本，并用高效液相色谱-紫外法分析其中双氯芬酸的含量。所给药的任何制剂均未报告有不良反应。几何平均试验/参比个体比率分别为：AUC(0 - 24小时)为92.8%，AUC(0 - 无穷大)为93.2%，Cmax为117.2%，Ke为131.0%，T1/2为76.2%。以变异系数（CV）表示的Cmax参数的变异性大于25%。由于AUC(0 - 24小时)平均比率的90%置信区间在食品药品监督管理局提议的80 - 125%区间内，因此可以得出结论，就吸收程度而言，双氯芬酸游离酸制剂与双氯芬酸树脂酸盐制剂生物等效。由于欧洲共同体机构接受Cmax的90%置信区间为70 - 143%，因此可以得出结论，单次给药后，就吸收速率和程度而言，双氯芬酸游离酸制剂与双氯芬酸树脂酸盐制剂生物等效。
